The analysis of individual intact eukaryotic cells, or populations of isolated cells, can be hindered due to many factors, including the morphology of the cell (e.g., differentiated neurons), the source of the cell (e.g., complex tissue), or the fact that the cells have been treated with a preservative or are otherwise in a non-viable or compromised state (e.g., frozen, fixed, paraffin embedded, attached to a slide, etc.). Such difficulties have resulted in a loss of valuable information that could be gained were the cells more amenable to manipulation. Among other advantages, the present disclosure provides methods and systems for isolating individual nuclei derived from a cell sample (e.g., fixed or frozen samples), thereby enabling the analysis of cell phenotypes and genotypes from cell sources that were previously considered of limited value.